tbuckley/cabot-search huggingface dataset:
The impact of maternal‐fetal omalizumab transfer on peanut‐specific responses in an ex vivo placental perfusion model
Authors: Akash Kothari, Birgit Hirschmugl, Jean‐Soo Lee, Birgit Pfaller, Klara Schmidthaler, Zsolt Szépfalusi, Christian Wadsack, Thomas Eiwegger
Journal: Allergy (2022)

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Ann Robinson’s research reviews—4 August 2022
Authors: Ann Robinson
Journal: BMJ (2022)

Nothing new under the sunThis US study of 200 people with poorly controlled type 2 diabetes (HbA1c>8.5% for over a year despite care in a diabetes clinic) found that a comprehensive telehealth intervention-including remote monitoring and support with diet, exercise, self management, medication, and mental health-improved HbA1c results at 12 months to a greater extent than a simpler intervention that only provided telemonitoring and care coordination (1.59% v 0.98%).Interestingly, the comprehensive intervention, which cost an extra $1519/patient/year to deliver, didn't improve weight loss or depression, although it did improve self-rated diabetes-related distress and self-care.So, a greater level of support by a trained healthcare professional resulted in better outcomes-no surprise there.
Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses
Authors: Jeroen M.J. Tas, Ja-Hyun Koo, Ying-Cing Lin, Zhenfei Xie, Jon M. Steichen, Abigail M. Jackson, Blake M. Hauser, Xuesong Wang, Christopher A. Cottrell, Jonathan L. Torres, John E. Warner, Kathrin H. Kirsch, Stephanie R. Weldon, Bettina Groschel, Bartek Nogal, Gabriel Ozorowski, Sandhya Bangaru, Nicole Phelps, Yumiko Adachi, Saman Eskandarzadeh, Michael Kubitz, Dennis R. Burton, Daniel Lingwood, Aaron G. Schmidt, Usha Nair, Andrew B. Ward, William R. Schief, Facundo D. Batista
Journal: Immunity (2022)

Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that the antibodies elicited during primary humoral responses shaped the naive B cell recruitment to GCs during secondary exposures. The antibodies from primary responses could either enhance or, conversely, restrict the GC participation of naive B cells: broad-binding, low-affinity, and low-titer antibodies enhanced recruitment, whereas, by contrast, the high titers of high-affinity, mono-epitope-specific antibodies attenuated cognate naive B cell recruitment. Thus, the directionality and intensity of that effect was determined by antibody concentration, affinity, and epitope specificity. Circulating antibodies can, therefore, be important determinants of antigen immunogenicity. Future vaccines may need to overcome-or could, alternatively, leverage-the effects of circulating primary antibodies on subsequent naive B cell recruitment.
Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein
Authors: Kamyab Javanmardi, Thomas H. Segall-Shapiro, Chia-Wei Chou, Daniel R. Boutz, Randall J. Olsen, Xuping Xie, Hongjie Xia, Pei-Yong Shi, Charlie D. Johnson, Ankur Annapareddy, Scott Weaver, James M. Musser, Andrew D. Ellington, Ilya J. Finkelstein, Jimmy D. Gollihar
Journal: Cell Host & Microbe (2022)
Protective antibodies and T cell responses to Omicron variant after the booster dose of BNT162b2 vaccine
Authors: Paul Naaber, Liina Tserel, Kadri Kangro, Marite Punapart, Epp Sepp, Virge Jürjenson, Jaanika Kärner, Liis Haljasmägi, Uku Haljasorg, Marilin Kuusk, Eve Sankovski, Anu Planken, Mart Ustav, Eva Žusinaite, Joachim M. Gerhold, Kai Kisand, Pärt Peterson
Journal: Cell Reports Medicine (2022)

The high number of mutations in the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes its immune escape. We report a longitudinal analysis of 111 vaccinated individuals for their antibody levels up to 6 months after the third dose of the BNT162b2 vaccine. After the third dose, the antibody levels decline but less than after the second dose. The booster dose remarkably increases the serum ability to block wild-type or Omicron variant spike protein's receptor-binding domain (RBD) interaction with the angiotensin-converting enzyme 2 (ACE2) receptor, and these protective antibodies persist 3 months later. Three months after the booster dose, memory CD4+ and CD8+ T cells to the wild-type and Omicron variant are detectable in the majority of vaccinated individuals. Our data show that the third dose restores the high levels of blocking antibodies and enhances T cell responses to Omicron.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2018)

Treating RAS-Driven CancersDrug development against RAS has focused on downstream kinases as RAS proteins are regarded undruggable.Xue and colleagues demonstrate that inhibition of MEK-activated JNK-JUN signaling through suppression of DUSP4 phosphatase activated HER receptor tyrosine kinases.HER activation stimulated the MAPK pathway, reducing the efficacy of MEK inhibition.Importantly, cancers that lost MAP3K1 or MAP2K4 failed to activate JNK-JUN, conferring sensitivity to MEK inhibition.Using a panel of 168 patientderived xenograft tumors, the authors showed that MAP3K1 and MAP2K4 mutational status was a strong predictor of response to MEK inhibition.Expert Commentary: MAP3K1 or MAP2K4 mutations are frequent in
Highlights of This Issue
Journal: Clinical Cancer Research (2018)

5FU-Enhanced PDT for Human Actinic KeratosesActinic keratoses (AK) are very common premalignant skin lesions (presquamous cell carcinoma) in patients with chronic sun damage.Recently, physicians have been empirically combining two treatment approaches, topical 5-fluorouracil (5FU) and photodynamic therapy (PDT), but without any scientific basis.In a mechanistic clinical study using surface fluorimetry and skin biopsies, Maytin and collea-
Continuous intra-abdominal pressure: is it ready for prime time?
Authors: Manu L. N. G. Malbrain, Bart L. De Keulenaer, Ashish K. Khanna
Journal: Intensive Care Medicine (2022)

Abdominal contents are primarily fluid in character so that pressure within this compartment follows Pascal's hydrostatic law.Intra-abdominal pressure (IAP) is the steady state pressure within the abdominal cavity and changes during respiration with an inspiratory increase [1].Mean perfusion pressure (MPP) is the difference between mean arterial pressure (MAP) and central venous pressure (CVP).Similarly abdominal perfusion pressure (APP) is calculated as the difference between MAP and IAP.MPP has been seen to be associated with progression of organ system injury [2]. Consensus definitionThe reference standard for intermittent IAP measurements is via the bladder with a maximal instillation volume of 25 mL of sterile saline.IAP should be expressed in mmHg and measured at end-expiration in the supine position after ensuring abdominal muscle contractions are absent and with the transducer zeroed at the level where the midaxillary line crosses the iliac crest and is approximately 5-7 mmHg in healthy and 10 mmHg in critically ill adults.IAH is defined by a sustained or repeated elevation in IAP ≥ 12 mmHg.ACS is defined as a sustained IAP > 20 mmHg that is associated with new organ dysfunction/failure [3].
ESO–ESMO fifth international consensus guidelines for breast cancer in young women (BCY5)
Authors: S. Paluch-Shimon, F. Cardoso, A.H. Partridge, O. Abulkhair, H.A. Azim, G. Bianchi-Micheli, M.J. Cardoso, G. Curigliano, K.A. Gelmon, O. Gentilini, N. Harbeck, B. Kaufman, S.B. Kim, Q. Liu, J. Merschdorf, P. Poortmans, G. Pruneri, E. Senkus, B. Sirohi, T. Spanic, V. Sulosaari, F. Peccatori, O. Pagani
Journal: Annals of Oncology (2022)
Risk of Parkinson Disease Among Adults With vs Without Posttraumatic Stress Disorder
Authors: Yael Barer, Gabriel Chodick, Nurit Glaser Chodick, Tanya Gurevich
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Posttraumatic stress disorder (PTSD) in elderly men may be associated with increased risk of Parkinson disease (PD); thus, this group of patients needs to be monitored closely for timely, customized treatment. <h3>Objective</h3> To evaluate the risk of PD in patients with PTSD compared with patients without PTSD. <h3>Design, Setting, and Participants</h3> This population-based, retrospective, cohort study used data from Maccabi Health Care Services (MHS), the second largest health plan in Israel, spanning from 2000 to 2019. Participants included MHS members born before 1970 who received a diagnosis of PTSD in 2000 to 2015. Patients with PTSD who had PD before their first diagnosis were excluded. Data analysis was performed from February to June 2022. <h3>Exposures</h3> Incident PTSD was denoted by at least 1 diagnosis (1) given by psychiatrists, psychologists, or neurologists; (2) hospital discharge diagnosis; or (3) registered as a chronic diagnosis (defined as such by the primary care physician). The index date was defined as first diagnosis for the patients with PTSD and for the corresponding patients without PTSD. <h3>Main Outcomes and Measures</h3> PD incident cases up to 2019 were ascertained by idiopathic PD diagnosis (1) given by a neurologist, (2) extracted from a hospital discharge report, or (3) registered as a chronic diagnosis. Patients with PD-like syndromes documentation after the last mention of PD were excluded. <h3>Results</h3> Of 8342 eligible patients, 8336 (99.9%) were matched to nonexposed patients in a 1:1 ratio by birth year and sex; 4303 patients (51.6%) were male, and the mean (SD) age at index was 55.8 (13.2) years. Patients with PTSD had a 1.48-fold (95% CI, 1.10-1.99) excess risk for PD, compared with patients without PTSD. An elevated risk of PD (hazard ratio, 1.95; 95% CI, 1.16-3.28) was recorded among men receiving a diagnosis of PTSD at age 72 years or older. <h3>Conclusions and Relevance</h3> These findings suggest that elderly men who receive a diagnosis of PTSD are at an increased risk of PD. Further studies are needed to corroborate these findings and to further assess the association of stress with PD risk.
Association Between Prostate-Specific Antigen Screening and Prostate Cancer Mortality Among Non-Hispanic Black and Non-Hispanic White US Veterans
Authors: Michael V. Sherer, Edmund M. Qiao, Nikhil V. Kotha, Alexander S. Qian, Brent S. Rose
Journal: JAMA Oncology (2022)

Black men have higher prostate cancer incidence and mortality than non-Hispanic White men. However, Black men have been underrepresented in clinical trials of prostate-specific antigen (PSA) screening; thus, there is a lack of data to guide screening recommendations for this population.To assess whether PSA screening is associated with reduced risk of prostate cancer-specific mortality (PCSM) among non-Hispanic Black men.This retrospective cohort study used data from the US Veterans Health Administration Informatics and Computing Infrastructure for men aged 55 to 69 years who self-identified as non-Hispanic Black or non-Hispanic White and were diagnosed with intermediate-, high-, or very high-risk prostate cancer from January 1, 2004, to December 31, 2017. Data were analyzed from August 2021 to March 2022.Prostate-specific antigen screening rate, defined as the percentage of years in which PSA screening was conducted during the 5 years before diagnosis of prostate cancer.The primary outcome was risk of PCSM among Black men and White men. The association between PSA screening and risk of PCSM was assessed using Fine-Gray regression analysis. Risk of PCSM was also assessed categorically among patients classified as having no prior PSA screening, some screening (less than annual), or annual screening in the 5 years before diagnosis.The study included 45 834 veterans (mean [SD] age, 62.7 [3.8] years), of whom 14 310 (31%) were non-Hispanic Black men and 31 524 (69%) were non-Hispanic White men. The PSA screening rate was associated with a lower risk of PCSM among Black men (subdistribution hazard ratio [sHR], 0.56; 95% CI, 0.41-0.76; P = .001) and White men (sHR, 0.58; 95% CI, 0.46-0.75; P = .001). On subset analysis, annual screening (vs some screening) was associated with a significant reduction in risk of PCSM among Black men (sHR, 0.65; 95% CI, 0.46-0.92; P = .02) but not among White men (sHR, 0.91; 95% CI, 0.74-1.11; P = .35).In this cohort study, PSA screening was associated with reduced risk of PCSM among non-Hispanic Black men and non-Hispanic White men. Annual screening was associated with reduced risk of PCSM among Black men but not among White men, suggesting that annual screening may be particularly important for Black men. Further research is needed to identify appropriate populations and protocols to maximize the benefits of PSA screening.
How to conduct a systematic review and meta-analysis of prognostic model studies
Authors: Johanna A.A. Damen, Karel G.M. Moons, Maarten van Smeden, Lotty Hooft
Journal: Clinical Microbiology and Infection (2022)

Prognostic models are typically developed to estimate the risk that an individual in a particular health state will develop a particular health outcome, to support (shared) decision making. Systematic reviews of prognostic model studies can help identify prognostic models that need to further be validated or are ready to be implemented in healthcare.To provide a step-by-step guidance on how to conduct and read a systematic review of prognostic model studies and to provide an overview of methodology and guidance available for every step of the review progress.Published, peer-reviewed guidance articles.We describe the following steps for conducting a systematic review of prognosis studies: 1) Developing the review question using the Population, Index model, Comparator model, Outcome(s), Timing, Setting format, 2) Searching and selection of articles, 3) Data extraction using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist, 4) Quality and risk of bias assessment using the Prediction model Risk Of Bias ASsessment (PROBAST) tool, 5) Analysing data and undertaking quantitative meta-analysis, and 6) Presenting summary of findings, interpreting results, and drawing conclusions. Guidance for each step is described and illustrated using a case study on prognostic models for patients with COVID-19.Guidance for conducting a systematic review of prognosis studies is available, but the implications of these reviews for clinical practice and further research highly depend on complete reporting of primary studies.
Safety and Sustained Efficacy of the Farnesoid X Receptor (FXR) Agonist Cilofexor Over a 96-Week Open-label Extension in Patients With PSC
Authors: Michael Trauner, Christopher L. Bowlus, Aliya Gulamhusein, Bilal Hameed, Stephen H. Caldwell, Mitchell L. Shiffman, Charles Landis, Andrew J. Muir, Andrew Billin, Jun Xu, Xiangyu Liu, Xiaomin Lu, Chuhan Chung, Robert P. Myers, Kris V. Kowdley
Journal: Clinical Gastroenterology and Hepatology (2022)
Reforming Patient Cost Sharing for Cancer Medications in Medicare Part D
Authors: Thomas J. Hwang, Aaron S. Kesselheim, Stacie B. Dusetzina
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
The Need for Electronic Health Records to Support Delivery of Behavioral Health Preventive Services
Authors: Alison N. Huffstetler, John Epling, Alex H. Krist
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A New Approach to Simplifying and Harmonizing Cancer Clinical Trials—Standardizing Eligibility Criteria
Authors: David E. Gerber, Harpreet Singh, Erin Larkins, Andrea Ferris, Patrick M. Forde, Wendy Selig, Upal Basu Roy
Journal: JAMA Oncology (2022)

Clinical trial sponsors rely on eligibility criteria to control the characteristics of patients in their studies, promote the safety of participants, and optimize the interpretation of results. However, in recent years, complex and often overly restrictive inclusion and exclusion criteria have created substantial barriers to patient access to novel therapies, hindered trial recruitment and completion, and limited generalizability of trial results. A LUNGevity Foundation working group developed a framework for lung cancer clinical trial eligibility criteria. The goals of this framework are to (1) simplify eligibility criteria, (2) facilitate stakeholders' (patients, clinicians, and sponsors) search for appropriate trials, and (3) harmonize trial populations to support intertrial comparisons of treatment effects.Clinicians and representatives from the pharmaceutical industry, the National Cancer Institute, the US Food and Drug Administration (FDA), the European Medicines Agency, and the LUNGevity Foundation undertook a process to identify and prioritize key items for inclusion in trial eligibility criteria. The group generated a prioritized library of terms to guide investigators and sponsors in the design of first-line, advanced non-small cell lung cancer clinical trials intended to support marketing application. These recommendations address disease stage and histologic features, enrollment biomarkers, performance status, organ function, brain metastases, and comorbidities. This effort forms the basis for a forthcoming FDA draft guidance for industry.As an initial step, the recommended cross-trial standardization of eligibility criteria may harmonize trial populations. Going forward, by connecting diverse stakeholders and providing formal opportunity for public input, the emerging FDA draft guidance may also provide an opportunity to revise and simplify long-standing approaches to trial eligibility. This work serves as a prototype for similar efforts now underway for other cancers.
Cardiovascular effects of incretins: focus on glucagon-like peptide-1 receptor agonists
Authors: Sten Madsbad, Jens J Holst
Journal: Cardiovascular Research (2022)

Abstract Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used to treat patients with type 2 diabetes since 2005 and have become popular because of the efficacy and durability in relation to glycaemic control in combination with weight loss in most patients. Today in 2022, seven GLP-1 RAs, including oral semaglutide are available for treatment of type 2 diabetes. Since the efficacy in relation to reduction of HbA1c and body weight as well as tolerability and dosing frequency vary between agents, the GLP-1 RAs cannot be considered equal. The short acting lixisenatide showed no cardiovascular benefits, while once daily liraglutide and the weekly agonists, subcutaneous semaglutide, dulaglutide, and efpeglenatide, all lowered the incidence of cardiovascular events. Liraglutide, oral semaglutide and exenatide once weekly also reduced mortality. GLP-1 RAs reduce the progression of diabetic kidney disease. In the 2019 consensus report from European Association for the Study of Diabetes/American Diabetes Association, GLP-1 RAs with demonstrated cardio-renal benefits (liraglutide, semaglutide and dulaglutide) are recommended after metformin to patients with established cardiovascular diseases or multiple cardiovascular risk factors. European Society of Cardiology suggests starting with a sodium-glucose cotransprter-2 inhibitor or a GLP-1 RA in drug naïve patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (CVD) or high CV Risk. However, the results from cardiovascular outcome trials (CVOT) are very heterogeneous suggesting that some GLP-1RAs are more suitable to prevent CVD than others. The CVOTs provide a basis upon which individual treatment decisions for patients with T2D and CVD can be made.
Regression Models for Ordinal Outcomes
Authors: Benjamin French, Matthew S. Shotwell
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal